SARS-CoV-2 Infection
Conditions
Keywords
COVID-19, Coronavirus disease 2019, Severe acute respiratory syndrome coronavirus 2, immunoglobulins, intravenous, subcutaneous, intramuscular
Brief summary
The primary objectives of this open-label trial were to evaluate the safety and pharmacokinetics (PK) of Anti-SARS-CoV-2 Immunoglobulin (Human) Investigational Product (COVID-HIG) administered intramuscularly (IM), subcutaneously (SC), or intravenously (IV) as a single dose in healthy adults 18-59 years of age with body mass index ≤35 kg/m\^2. Prior studies examined IV administration, and the secondary objective of the present study was to compare PK among the three administration routes. No placebo group was included in the phase 1 randomized design. The exploratory objective was to evaluate disease severity in participants that became positive for SARS-CoV-2.
Detailed description
Eligible participants were randomized in two cohorts to receive COVID-HIG by IM, SC or IV in a 1:1:1 ratio and were stratified based on baseline SARS-CoV-2 IgG antibody status (low seropositive/seronegative; high seropositives were excluded). Up to 36 participants were planned to be enrolled and dosed in the study. A protocol amendment truncated the study to 23 randomized participants due to the impact of high circulating SARS-CoV-2 omicron cases on enrollment and participant retention. Participants were planned to be followed through Day 85 (approximately three half-lives), but the protocol was amended to shorten the study length to Day 57 due to timeline and PK considerations. The third substantial protocol amendment change was to remove the planned pseudovirus neutralization assay from the study due to its low sensitivity, limiting the PK analysis to the S-protein binding IgG immunoassay. PK time points included predose and postdose (from end of infusion/injection) 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, Days 2, 3, 4, 6, 8, 15, 29, 43 and 57. Nasopharyngeal swabs for SARS-CoV-2 were collected throughout the study. Per protocol, participants who became SARS-CoV-2 positive could not be assessed for PK at time points after testing positive, as the assay could not distinguish COVID-HIG from native antibodies. Participants who became SARS-CoV-2 positive during the study had disease severity assessed using an Ordinal Outcome Scale and followed via telemedicine through the end of the study.
Interventions
BIOLOGICALCOVID-HIG
Anti-SARS-CoV-2 Immunoglobulin (Human) \[COVID-HIG\] is a purified liquid immunoglobulin G (IgG) preparation
Sponsors
United States Department of Defense
Emergent BioSolutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants in two cohorts will be enrolled and assigned equally to one of three study arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
1. Able and willing to provide written informed consent (voluntarily signed by the participant) prior to performing study procedures. 2. Females and males 18-59 years of age. 3. Have a body mass index (BMI) less than or equal to 35.0 kg/m\^2 4. Healthy, based on medical history (no chronic disease, no chronic therapy, no ongoing acute condition within four weeks prior to dosing), normal physical examination (no clinically significant findings in the opinion of the investigator), and screening laboratory assessments (no clinically significant findings in the opinion of the investigator). 5. No clinical symptoms suspicious for COVID-19 infection, as well as SARS-CoV-2 Immunoglobulin M (IgM) antibody negative and no laboratory evidence of current SARS-CoV-2 infection (i.e., reverse transcription polymerase chain reaction (RT-PCR) negative for SARS-CoV-2) at Screening. 6. Females must not be pregnant, or trying to become pregnant as demonstrated by either of the following A or B: A. Not of childbearing potential: surgically sterile (at least six weeks post bilateral salpingectomy, bilateral oophorectomy, or hysterectomy); or post-menopausal (history of ≥12 consecutive months without menses prior to randomization in the absence of other pathologic or physiologic causes and confirmed by follicle stimulating hormone \[FSH\] level ≥40 mIU/mL) OR B. Women of childbearing potential who are not planning to be pregnant during the study period who meet all of criteria i-iii: i. Negative serum pregnancy test at the Screening Visit. ii. Negative urine pregnancy test on Day 1 (a positive test will result in discontinuation from intervention). iii. Using one of the following highly effective methods of contraception during the study: 1. Combined estrogen and progestogen, or progestogen-only hormonal contraception associated with inhibition of ovulation (e.g., implants, pills, patches) initiated ≥30 days prior to Study Day 1. 2. Intrauterine device (IUD) or hormone releasing intrauterine system (IUS) inserted ≥30 days prior to Study Day 1. 7. Participant understands and agrees to comply with planned study procedures.
Exclusion criteria
1. Use of any investigational product within 30 days or SARS-CoV-2 monoclonal antibodies and COVID-19 convalescent plasma within 90 days prior to Screening or anticipated receipt during the study follow-up period, or participant plans to participate in another clinic study during the study period. 2. Receipt of 1 or 2 doses COVID-19 vaccine within 60 days prior to screening or during the study follow-up period. 3. SARS-CoV-2 IgG antibody levels \>80 AU/mL as determined by the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG antibody assay. 4. Screening clinical laboratory test result greater than the laboratory's upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), random glucose, total and/or direct bilirubin, blood urea nitrogen (BUN), or creatinine. Other serum chemistry parameters that are not within the reference range will not be considered exclusionary unless deemed clinically significant by the principal investigator. 5. Positive laboratory evidence of current infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV). Note: Positive anti-HCV antibody result along with a negative HCV PCR would NOT be exclusionary. 6. History of allergy or hypersensitivity to blood or plasma products or to COVID-HIG excipients (proline, PS80). 7. History of allergy to latex or rubber. 8. History of hemolytic anemia. 9. History of Immunoglobulin A (IgA) deficiency. 10. Receipt of any blood product within the past 12 months. 11. Plasma donation within 7 days or blood loss/donation (\>450 mL) within 56 days of dosing. 12. History of known congenital or acquired immunodeficiency or receipt of immunosuppressive therapy (e.g., prednisone or equivalent for more than two consecutive weeks within the past three months). 13. History of thrombosis or hypercoagulable state with increased risk of thrombosis. 14. Receipt of a live vaccine within 30 days prior to screening or anticipated receipt of a live vaccine during the study period. 15. Currently pregnant, breastfeeding, or planning to become pregnant during the study. 16. History of, or suspected substance abuse problem (including alcohol). 17. Any planned elective surgery or procedure during the follow-up period that impacts study compliance. 18. Other condition which may place participant at increased risk due to participation in the study or may impact study compliance as determined by the investigator. 19. An opinion of the investigator (or designee) that it would not be in the best interest of the individual to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIG | Day 1 to Day 29 | The observed trough concentration of SARS-CoV-2 binding IgG antibodies 28 days after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, and Day 29. |
| Participants With AEs and SAEs After Study Treatment | Day 0 to Day 57 | Number of participants with adverse events (AEs) and serious adverse events (SAEs) up to 56 days post-administration of a single dose of COVID-HIG. |
| Total Number of AEs and SAEs After Study Treatment | Day 0 to Day 57 | Number of adverse events (AEs) and serious adverse events (SAEs) in all participants reporting AEs/SAEs up to 56 days post-dosing. |
| Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-last) of SARS-CoV-2 Antibodies After Dose of COVID-HIG | Day 1 to Day 57 | The area under the concentration-time curve from time 0 to the last quantifiable concentration of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57. |
| Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | Day 1 to Day 57 | Area under the concentration-time curve from time 0 to the last quantifiable concentration plus the additional area extrapolated to infinity of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57. |
| Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIG | Day 1 to Day 57 | The Cmax of SARS-CoV-2 binding IgG antibodies observed after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57. |
| Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIG | Day 1 to Day 57 | Time at which Cmax occurs (Tmax) after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57. |
| Participants With Adverse Events (AEs) up to 72 Hours Post-dosing | 72 hours | Number of participants with AEs and severity of AEs up to 72 hours post-dosing. |
| Participants With Adverse Events That Led to Discontinuation or Temporary Suspension of Study Treatment | Day 1 | Number of participants and severity of AEs that led to discontinuation or temporary suspension of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIG. | Day 1 to Day 29 | AUC from time 0 to 28 days of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, and Day 29. |
| Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIG | Day 1 to Day 15 | AUC from time 0 to 14 days (AUC0-14d) of SARS-CoV-2 binding IgG antibodies after COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, and Day 15. |
| Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIG | Day 1 to Day 57 | The apparent terminal elimination half-life (T1/2) after dose of COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57. |
| Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIG | Day 1 to Day 57 | The systemic clearance (CL) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIG. . Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57. |
| Pharmacokinetic Parameter of Volume of Distribution (Vz) After Dose of COVID-HIG | Day 1 to Day 57 | The volume of distribution (Vz) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Comparative Bioavailability: Area Under the Concentration-time Curve (AUC) From Time 0 to Last (AUC0-last) Ratios Between Administration Routes | Day 1 to Day 57 | AUC0-last ratios (bioavailability) compared between routes for comparable dose levels (COVID-HIG IM to SC; SC to IV; and IM to IV). Least square mean estimates and 90% confidence intervals were derived from ANOVA model with AUC0-last as dependent variable and administration route as fixed effect. Comparative bioavailability was defined as within \[80%, 125%\]. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COVID-HIG Intramuscular (IM) Eligible subjects will be randomized to receive an 8.5mL dose of COVID-HIG by IM injections.
COVID-HIG: COVID-HIG is a purified immunoglobulin G (IgG) liquid preparation containing antibodies (including neutralizing antibodies) to SARS-CoV-2.
COVID-HIG: Anti-SARS-CoV-2 Immunoglobulin (Human) \[COVID-HIG\] is a purified liquid immunoglobulin G (IgG) preparation | 7 |
| COVID-HIG Subcutaneous (SC) Eligible subjects will be randomized to receive an 8.5mL dose of COVID-HIG by SC injections.
COVID-HIG: COVID-HIG is a purified immunoglobulin G (IgG) liquid preparation containing antibodies (including neutralizing antibodies) to SARS-CoV-2.
COVID-HIG: Anti-SARS-CoV-2 Immunoglobulin (Human) \[COVID-HIG\] is a purified liquid immunoglobulin G (IgG) preparation | 8 |
| COVID-HIG Intravenous (IV) Eligible subjects will be randomized to receive an 8.5mL dose of COVID-HIG by IV infusion.
COVID-HIG: COVID-HIG is a purified immunoglobulin G (IgG) liquid preparation containing antibodies (including neutralizing antibodies) to SARS-CoV-2.
COVID-HIG: Anti-SARS-CoV-2 Immunoglobulin (Human) \[COVID-HIG\] is a purified liquid immunoglobulin G (IgG) preparation | 7 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | COVID-HIG Intravenous (IV) | COVID-HIG Subcutaneous (SC) | COVID-HIG Intramuscular (IM) |
|---|---|---|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 11.8 | 32.4 years STANDARD_DEVIATION 9.2 | 36.3 years STANDARD_DEVIATION 13 | 45.9 years STANDARD_DEVIATION 9.7 |
| Baseline body mass index | 26.46 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 3.96 | 25.56 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 3.49 | 25.09 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 4.12 | 28.94 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 3.48 |
| Baseline SARS-CoV-2 Antibody Status Seronegative | 12 Participants | 4 Participants | 4 Participants | 4 Participants |
| Baseline SARS-CoV-2 Antibody Status Seropositive | 10 Participants | 3 Participants | 4 Participants | 3 Participants |
| Baseline weight | 75.44 kilograms STANDARD_DEVIATION 13.96 | 73.69 kilograms STANDARD_DEVIATION 7.62 | 67.29 kilograms STANDARD_DEVIATION 13.78 | 86.51 kilograms STANDARD_DEVIATION 12.95 |
| Enrollment per Study Site US6001 (Miami, FL) | 12 Participants | 3 Participants | 5 Participants | 4 Participants |
| Enrollment per Study Site US6002 (Springfield, MO) | 10 Participants | 4 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 3 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 4 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 168.43 centimeters STANDARD_DEVIATION 7.3 | 170.14 centimeters STANDARD_DEVIATION 6.28 | 163.31 centimeters STANDARD_DEVIATION 7.94 | 172.57 centimeters STANDARD_DEVIATION 3.88 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 7 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Female | 10 Participants | 2 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 5 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 6 / 7 | 3 / 8 | 4 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 | 0 / 7 |
Outcome results
Primary
Participants With Adverse Events (AEs) up to 72 Hours Post-dosing
Number of participants with AEs and severity of AEs up to 72 hours post-dosing.
Time frame: 72 hours
Population: Safety population includes all participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Participants With Adverse Events (AEs) up to 72 Hours Post-dosing | 2 Participants |
| COVID-HIG Subcutaneous (SC) | Participants With Adverse Events (AEs) up to 72 Hours Post-dosing | 1 Participants |
| COVID-HIG Intravenous (IV) | Participants With Adverse Events (AEs) up to 72 Hours Post-dosing | 2 Participants |
Primary
Participants With Adverse Events That Led to Discontinuation or Temporary Suspension of Study Treatment
Number of participants and severity of AEs that led to discontinuation or temporary suspension of study treatment.
Time frame: Day 1
Population: Safety population includes all participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Participants With Adverse Events That Led to Discontinuation or Temporary Suspension of Study Treatment | 0 Participants |
| COVID-HIG Subcutaneous (SC) | Participants With Adverse Events That Led to Discontinuation or Temporary Suspension of Study Treatment | 0 Participants |
| COVID-HIG Intravenous (IV) | Participants With Adverse Events That Led to Discontinuation or Temporary Suspension of Study Treatment | 0 Participants |
Primary
Participants With AEs and SAEs After Study Treatment
Number of participants with adverse events (AEs) and serious adverse events (SAEs) up to 56 days post-administration of a single dose of COVID-HIG.
Time frame: Day 0 to Day 57
Population: Safety population includes all participants who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| COVID-HIG Intramuscular (IM) | Participants With AEs and SAEs After Study Treatment | Number of participants with any AE | 6 Participants |
| COVID-HIG Intramuscular (IM) | Participants With AEs and SAEs After Study Treatment | Number of participants with any SAE | 0 Participants |
| COVID-HIG Subcutaneous (SC) | Participants With AEs and SAEs After Study Treatment | Number of participants with any AE | 3 Participants |
| COVID-HIG Subcutaneous (SC) | Participants With AEs and SAEs After Study Treatment | Number of participants with any SAE | 0 Participants |
| COVID-HIG Intravenous (IV) | Participants With AEs and SAEs After Study Treatment | Number of participants with any AE | 4 Participants |
| COVID-HIG Intravenous (IV) | Participants With AEs and SAEs After Study Treatment | Number of participants with any SAE | 0 Participants |
Primary
Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV
Area under the concentration-time curve from time 0 to the last quantifiable concentration plus the additional area extrapolated to infinity of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample, with samples occurring after a positive SARS-CoV-2 test result excluded).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | 8042.38 h*AU/mL |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | 6875.52 h*AU/mL |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | 19212.18 h*AU/mL |
Primary
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-last) of SARS-CoV-2 Antibodies After Dose of COVID-HIG
The area under the concentration-time curve from time 0 to the last quantifiable concentration of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample, with samples occurring after a positive SARS-CoV-2 test result excluded).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-last) of SARS-CoV-2 Antibodies After Dose of COVID-HIG | 6435.44 h*Alliance Units (AU)/mL |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-last) of SARS-CoV-2 Antibodies After Dose of COVID-HIG | 9560.60 h*Alliance Units (AU)/mL |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-last) of SARS-CoV-2 Antibodies After Dose of COVID-HIG | 11883.46 h*Alliance Units (AU)/mL |
Primary
Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIG
The Cmax of SARS-CoV-2 binding IgG antibodies observed after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample, with samples occurring after a positive SARS-CoV-2 test result excluded).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIG | 17.02 AU/mL |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIG | 16.24 AU/mL |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIG | 56.88 AU/mL |
Primary
Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIG
Time at which Cmax occurs (Tmax) after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample, with samples occurring after a positive SARS-CoV-2 test result excluded).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIG | 174.71 hours | Standard Deviation 221.13 |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIG | 201.01 hours | Standard Deviation 213.76 |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIG | 1.53 hours | Standard Deviation 0.53 |
Primary
Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIG
The observed trough concentration of SARS-CoV-2 binding IgG antibodies 28 days after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, and Day 29.
Time frame: Day 1 to Day 29
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples up to Day 29.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIG | 3.67 AU/mL |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIG | 7.55 AU/mL |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIG | 8.15 AU/mL |
Primary
Total Number of AEs and SAEs After Study Treatment
Number of adverse events (AEs) and serious adverse events (SAEs) in all participants reporting AEs/SAEs up to 56 days post-dosing.
Time frame: Day 0 to Day 57
Population: Safety population includes all participants who received any amount of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| COVID-HIG Intramuscular (IM) | Total Number of AEs and SAEs After Study Treatment | Total number of adverse events (AEs) for all participants reporting AEs | 9 Events |
| COVID-HIG Intramuscular (IM) | Total Number of AEs and SAEs After Study Treatment | Total number of SAEs for all participants reporting SAEs | 0 Events |
| COVID-HIG Subcutaneous (SC) | Total Number of AEs and SAEs After Study Treatment | Total number of adverse events (AEs) for all participants reporting AEs | 5 Events |
| COVID-HIG Subcutaneous (SC) | Total Number of AEs and SAEs After Study Treatment | Total number of SAEs for all participants reporting SAEs | 0 Events |
| COVID-HIG Intravenous (IV) | Total Number of AEs and SAEs After Study Treatment | Total number of SAEs for all participants reporting SAEs | 0 Events |
| COVID-HIG Intravenous (IV) | Total Number of AEs and SAEs After Study Treatment | Total number of adverse events (AEs) for all participants reporting AEs | 9 Events |
Secondary
Pharmacokinetic Parameter of Volume of Distribution (Vz) After Dose of COVID-HIG
The volume of distribution (Vz) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetic Parameter of Volume of Distribution (Vz) After Dose of COVID-HIG | 0.75 mL |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetic Parameter of Volume of Distribution (Vz) After Dose of COVID-HIG | 0.93 mL |
| COVID-HIG Intravenous (IV) | Pharmacokinetic Parameter of Volume of Distribution (Vz) After Dose of COVID-HIG | 0.35 mL |
Secondary
Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIG
The apparent terminal elimination half-life (T1/2) after dose of COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIG | 505.50 hours | Standard Deviation 128.13 |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIG | 535.70 hours | Standard Deviation 61.09 |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIG | 673.90 hours | Standard Deviation 356.02 |
Secondary
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIG
AUC from time 0 to 14 days (AUC0-14d) of SARS-CoV-2 binding IgG antibodies after COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, and Day 15.
Time frame: Day 1 to Day 15
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples up until Day 15.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIG | 12057.04 h*AU/mL |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIG | 11118.31 h*AU/mL |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIG | 11883.46 h*AU/mL |
Secondary
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIG.
AUC from time 0 to 28 days of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, and Day 29.
Time frame: Day 1 to Day 29
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples up to Day 29.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIG. | 14610.82 h*AU/mL |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIG. | 14624.92 h*AU/mL |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIG. | 12182.14 h*AU/mL |
Secondary
Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIG
The systemic clearance (CL) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIG. . Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COVID-HIG Intramuscular (IM) | Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIG | 0.0010 mL/h | Standard Deviation 0 |
| COVID-HIG Subcutaneous (SC) | Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIG | 0.0010 mL/h | Standard Deviation 0 |
| COVID-HIG Intravenous (IV) | Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIG | 0.0010 mL/h | Standard Deviation 0.0006 |
Other Pre-specified
Comparative Bioavailability: Area Under the Concentration-time Curve (AUC) From Time 0 to Last (AUC0-last) Ratios Between Administration Routes
AUC0-last ratios (bioavailability) compared between routes for comparable dose levels (COVID-HIG IM to SC; SC to IV; and IM to IV). Least square mean estimates and 90% confidence intervals were derived from ANOVA model with AUC0-last as dependent variable and administration route as fixed effect. Comparative bioavailability was defined as within \[80%, 125%\].
Time frame: Day 1 to Day 57
Population: The PK population included all subjects who received COVID-HIG and had an adequate set of evaluable PK samples. In each arm, there were n=7 in the COVID-HIG IM arm, n=8 in the COVID-HIG SC arm and n=7 in the COVID-HIG IV arm. The overall participants analyzed per group as indicated in this bioavailability comparison is the sum of each of the respective groups indicated in the title/description.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COVID-HIG Intramuscular (IM) | Comparative Bioavailability: Area Under the Concentration-time Curve (AUC) From Time 0 to Last (AUC0-last) Ratios Between Administration Routes | 0.67 ratio |
| COVID-HIG Subcutaneous (SC) | Comparative Bioavailability: Area Under the Concentration-time Curve (AUC) From Time 0 to Last (AUC0-last) Ratios Between Administration Routes | 0.54 ratio |
| COVID-HIG Intravenous (IV) | Comparative Bioavailability: Area Under the Concentration-time Curve (AUC) From Time 0 to Last (AUC0-last) Ratios Between Administration Routes | 0.80 ratio |